CAS OpenIR  > 中科院上海原子核所2003年前
Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein
Li, HT; Lin, DH; Luo, XY; Zhang, F(张峰); Ji, LN; Du, HN; Song, GQ; Hu, J(胡钧); Zhou, JW; Hu, HY
2005
Source PublicationFEBS JOURNAL
ISSN1742-464X
Volume272Issue:14
AbstractFibrillization of alpha-synuclein (alpha-Syn) is closely associated with the formation of Lewy bodies in neurons and dopamine (DA) is a potent inhibitor for the process, which is implicated in the causative pathogenesis of Parkinson's disease (PD). To elucidate any molecular mechanism that may have biological relevance, we tested the inhibitory abilities of DA and several analogs including chemically synthetic and natural polyphenols in vitro. The MS and NMR characterizations strongly demonstrate that DA and its analogs inhibit alpha-Syn fibrillization by a mechanism where the oxidation products (quinones) of DA analogs react with the amino groups of alpha-Syn chain, generating alpha-Syn-quinone adducts. It is likely that the amino groups of alpha-Syn undergo nucleophilic attack on the quinone moiety of DA analogs to form imino bonds. The covalently cross-linked alpha-Syn adducts by DA are primarily large molecular mass oligomers, while those by catechol and p-benzoquinone (or hydroquinone) are largely monomers or dimers. The DA quinoprotein retains the same cytotoxicity as the intact alpha-Syn, suggesting that the oligomeric intermediates are the major elements that are toxic to the neuronal cells. This finding implies that the reaction of alpha-Syn with DA is relevant to the selective dopaminergic loss in PD.
Indexed BySCI
Language英语
Funding Project原子核所项目组
WOS IDWOS:000230293100016
Citation statistics
Cited Times:86[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/12954
Collection中科院上海原子核所2003年前
Recommended Citation
GB/T 7714
Li, HT,Lin, DH,Luo, XY,et al. Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein[J]. FEBS JOURNAL,2005,272(14).
APA Li, HT.,Lin, DH.,Luo, XY.,Zhang, F.,Ji, LN.,...&Hu, HY.(2005).Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein.FEBS JOURNAL,272(14).
MLA Li, HT,et al."Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein".FEBS JOURNAL 272.14(2005).
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